3 CHAPTER 3 50 Abstract The cerebrospinal fluid (CSF) is regarded a suitable body fluid for metabolomics studies on central nervous system (CNS) disorders as it, due to its close proximity, best reflects changes in the brain. However, as repeated CSF sampling is not patient-centered, blood sampling should be considered the better alternative for, for instance, longitudinal studies. A relevant question then is how well metabolites in blood and CSF correlate. Therefore, we here studied concentrations of amines, including amino acids and biogenic amines in human blood plasma and CSF to investigate in control individuals and patients with migraine how these fluids are associated. Amines were measured using a validated ultra-performance liquid chromatography mass spectrometry (UPLCMS) platform. Using single-metabolite correlation, a minority of 39 amines (4/39, 10.3%) had a correlation coefficient ≥ .70. Ratio correlations were significantly better than single-metabolite correlations for 308 of 741 (41.5%) of amine combinations after multiple testing correction (FDR < .05). Primarily, amino acids showed high correlation when studied as ratios (i.e. L-leucine/Lmethionine, L-leucine/L-asparagine, L-valine/L-phenylalanine), likely because these ratios are tightly regulated by blood-brain barrier transport systems. We extended our analyses to migraine. Our analyses revealed that some amine ratios seem affected in participants with migraine when compared to healthy controls. KEYWORDS: Omics, comparison, neurotransmitters, migraine, ultra-performance liquid chromatography mass spectrometry (UPLC-MS)
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